Human blood group systems

The term human blood group systems is defined by the International Society of Blood Transfusion (ISBT) as systems in the human species where cell-surface antigens—in particular, those on blood cells—are "controlled at a single gene locus or by two or more very closely linked homologous genes with little or no observable recombination between them",[1] and include the common ABO and Rh (Rhesus) antigen systems, as well as many others; 44 human systems are identified as of December 2022.[2]

For the an overview of the main blood types and their clinical significance, see Blood type.

Table of systems and classifications
ISBT No.[3] System name System symbol Structure / function Chromosome Antigens Notes
001 ABO ABO Carbohydrate (N-Acetylgalactosamine, galactose). 9q34.2 A, B, H Mainly elicit IgM antibody reactions, although anti-H is very rare, see the Hh antigen system (Bombay phenotype, ISBT #18).
002 MNS MNS GPA / GPB (glycophorins A and B). 4q31.21 M, N, S, s
003 P1PK P Glycolipid 22q13.2 P1, P, and Pk
004 Rhesus RH Protein and glucose. 1p36.11 C, c, D, E, e There is no "d" antigen; lowercase "d" indicates the absence of D.
005 Lutheran LU Protein (member of the immunoglobulin superfamily). 19q13.32 21 antigens
006 Kell KEL Glycoprotein. 7q34 K, k, Kpa, Kpb, Jsa and Jsb [4]
007 Lewis LE Carbohydrate (fucose residue). 19p13.3 Mainly Lea and Leb Associated with tissue ABH antigen secretion.
008 Duffy FY Protein (chemokine receptor). 1q23.2 Mainly Fya and Fyb Individuals lacking Duffy antigens altogether are immune to malaria caused by Plasmodium vivax and Plasmodium knowlesi.
009 Kidd JK Protein (urea transporter). 18q12.3 Jka and Jkb
010 Diego DI Glycoprotein (band 3, AE 1, or anion exchange). 17q21.31 Positive blood is found only among East Asians and Native Americans.
011 Yt YT Protein (AChE, acetylcholinesterase). 7q22.1
012 XG XG Glycoprotein. Xp22.33
013 Scianna SC Glycoprotein. 1p34.2
014 Dombrock DO Glycoprotein (fixed to cell membrane by GPI, or glycosyl-phosphatidyl-inositol). 12p12.3
015 Colton CO Aquaporin 1. 7p14.3 Mainly Co(a) and Co(b)
016 Landsteiner-Wiener LW Protein (member of the immunoglobulin superfamily). 19p13.2
017 Chido/Rodgers CH C4A C4B (complement fractions). 6p21.3
018 Hh H Carbohydrate (fucose residue). 19q13.33
019 XK XK Glycoprotein. Xp21.1
020 Gerbich GE GPC / GPD (Glycophorins C and D). 2q14.3
021 Cromer CROM Glycoprotein (DAF or CD55, regulates complement fractions C3 and C5, attached to the membrane by GPI). 1q32.2
022 Knops KN Glycoprotein (CR1 or CD35, immune complex receptor). 1q32.2
023 Indian IN Glycoprotein (CD44 adhesion function?). 11p13
024 Ok OK Glycoprotein (CD147). 19p13.3
025 Raph RAPH Transmembrane glycoprotein. 11p15.5
026 JMH JMH Protein (fixed to cell membrane by GPI). Also known as Semaphorin 7A or CD108. 15q24.1
027 Ii I Branched (I) / unbranched (i) polysaccharide. 6p24.2
028 Globoside GLOB Glycolipid. Antigen P. 3q26.1
029 GIL GIL Aquaporin 3. 9p13.3
030 Rh-associated glycoprotein RHAg Rh-associated glycoprotein. 6p21-qter
031 Forssman FORS Globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (GBGT1). 9q34.13
032 Langereis[5] LAN ABCB6, human ATP-binding cassette (ABC) transporter, mitochondrial porphyrin transporter.[5] 2q36
033 Junior JR ABCG2. Multi-drug transporter protein. 4q22
034 Vel Vel Human red cell antigens. 1p36.32
035 CD59 CD59 — 11p13
036 Augustine AUG Protein (transporter).[6] 6p21.1
037 KANNO[7][8] PRNP — 20p13
038 SID SID 17q21.32
039 CTL2 CTL2 19p13.2
040 PEL PEL 13q32.1
041 MAM MAM 19q13.33
042 EMM EMM 4p16.3
043 ABCC1 ABCC1 16p13.11
044 Er[9] Er Protein Era, Erb, Er3, Er4, and Er5 Illustrates potential antigenicity of low abundance membrane proteins and contributes to understanding of in vivo characteristics of the Piezo1 protein in transfusion biology

Antibodies

Following is a comparison of clinically relevant characteristics of antibodies against the main human blood group systems:[10]

ABORhKellDuffyKiddLutheranMNSLewisPIi
Most common in immediate hemolytic transfusion reactions AYesFyaJka
Most common in delayed hemolytic transfusion reactions E,D,CJka
Most common in hemolytic disease of the newborn YesD,CYes
Commonly produce intravascular hemolysis YesYesYes
Reactive at room temperature YesM,NLea, LebP1
Nearly always clinically insignificant YesM,NYesP1
Naturally occurring YesYesM,NYesYesYes
Enhanced by ficain[11] and papain[12] YesYesYesYesP1Yes
Destroyed by ficain[11] and papain[12] Fya, Fyb YesYes
Displaying dosage
Further information: Blood compatibility testing
 Cc, EeYesYesYes

Compatibility testing
Main article: Blood compatibility testing
Interpretation of antibody panel to detect patient antibodies towards the most relevant human blood group systems

Blood compatibility testing is performed before blood transfusion, including matching of the ABO blood group system and the Rh blood group system, as well as screening for recipient antibodies against other human blood group systems. Blood compatibility testing is also routinely performed on pregnant women and on the cord blood from newborn babies, because incompatibility puts the baby at risk for developing hemolytic disease of the newborn.[13][14] It is also used before hematopoietic stem cell transplantation, as it may be responsible for some cases of acute graft-versus-host disease.[15]

Other human blood group systems than ABO and Rh have a relatively small risk of complications when blood is mixed.[16] Therefore, in emergencies such as major hemorrhage, the urgency of transfusion can exceed the need for compatibility testing against other blood group systems (and potentially Rh as well).[16] Also, blood compatibility testing beyond ABO and Rh is generally limited to antibody detection (not necessarily including forward typing). Still, in Europe, females who require blood transfusions are often typed for the K and extended Rh antigens to prevent sensitization to these antigens, which could put them at risk for developing hemolytic disease of the newborn during pregnancy.[17]

When needing to give red blood cell transfusion to a patient, the presence of clinically significant antibodies produced by the patient can be detected by mixing patient serum with 2 to 4 "screening" or "control" red blood cells that together display essentially all relevant antigens. If any of these mixes display a reaction (evidence of patient antibodies binding to the screening red blood cells), a more extensive antibody panel is warranted (as imaged at right). [18]

References
  1. ISBT (2016). "International Society for Blood Transfusion (ISBT) Committee on Terminology for Red Cell Surface Antigens, Terminology Home Page". Archived from the original on 3 March 2016. Retrieved 20 February 2016.
  2. "Red Cell Immunogenetics and Blood Group Terminology". International Society of Blood Transfusion. 2023. Archived from the original on 2 February 2022. Retrieved 25 April 2023.
  3. ISBT (2021). "Table of Blood Group Systems v 10.0 (June 2021)" (PDF). International Society of Blood Transfusion. Archived (PDF) from the original on 15 January 2022. Retrieved 11 February 2022.
  4. Smart, E.; Armstrong, B. (2008). "Blood group systems". ISBT Science Series. 3 (2): 68–92. doi:10.1111/j.1751-2824.2008.00188.x. ISSN 1751-2816.
  5. Helias, V.; Saison, C.; Ballif, B.A.; Peyrard, T.; Takahashi, J.; Takahashi, H.; Tanaka, M.; Deybach, J.C.; Puy, H.; Le Gall, M.; Sureau, C.; Pham, B.N.; Le Pennec, P.Y.; Tani, Y.; Cartron, J.P.; Arnaud, L. (2012). "ABCB6 is Dispensable for Erythropoiesis and Specifies the New Blood Group System Langereis". Nature Genetics. 44 (2, January 15): 170–173. doi:10.1038/ng.1069. PMC 3664204. PMID 22246506. [Quoting Abstract: The human ATP-binding cassette (ABC) transporter ABCB6 has been described as a mitochondrial porphyrin transporter essential for heme biosynthesis, but it is also suspected to contribute to anticancer drug resistance, as do other ABC transporters located at the plasma membrane. We identified ABCB6 as the genetic basis of the Lan blood group antigen expressed on red blood cells but also at the plasma membrane of hepatocellular carcinoma (HCC) cells, and we established that ABCB6 encodes a new blood group system (Langereis, Lan). Targeted sequencing of ABCB6 in 12 unrelated individuals of the Lan(-) blood type identified 10 different ABCB6 null mutations. This is the first report of deficient alleles of this human ABC transporter gene. Of note, Lan(-) (ABCB6(-/-)) individuals do not suffer any clinical consequences, although their deficiency in ABCB6 may place them at risk when determining drug dosage.]
  6. Daniels, G.; Ballif, B. A.; Helias, V.; Saison, C.; Grimsley, S.; Mannessier, L.; Hustinx, H.; Lee, E.; et al. (20 April 2015). "Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization". Blood. 125 (23): 3651–3654. doi:10.1182/blood-2015-03-631598. PMC 4458803. PMID 25896650.
  7. National Center for Global Health and Medicine, Japanese Red Cross Society, Fukushima Medical University and Japan Agency for Medical Research and Development (2019-08-05) 新たなヒト血液型「KANNO」の国際認定―国立国際医療研究センターなど、日本の研究グループとして初めての登録― (in Japanese)
  8. "Omae, Y.; Ito, S.; Takeuchi, M.; Isa, K.; Ogasawara, K.; Kawabata, K.; Oda, A.; Kaito, S.; Tsuneyama, H.; Uchikawa, M.; Wada, I.; Ohto, H.; Tokunaga, K. (2019). "Integrative genome analysis identified the KANNO blood group antigen as prion protein" Transfusion. 2019 Jul;59(7):2429-2435. DOI:10.1111/trf.15319. Epub 2019 Apr 24.
  9. Karamatic Crew, Vanja; Tilley, Louise A; Satchwell, Timothy J; AlSubhi, Samah A; Jones, Benjamin; Spring, Frances A; Walser, Piers J; Martins Freire, Catarina; Murciano, Nicoletta; Rotordam, Maria Giustina; Woestmann, Svenja J; Hamed, Marwa; Alradwan, Reem; AlKhrousey, Mouza; Skidmore, Ian; Lewis, Sarah; Hussain, Shimon; Jackson, Jane; Latham, Tom; Kilby, Mark D; Lester, William Arthur; Becker, Nadine; Rapedius, Markus; Toye, Ashley Mark; Thornton, Nicole M (19 September 2022). "Missense mutations in PIEZO1, encoding the Piezo1 mechanosensor protein, define the Er red blood cell antigens". Blood. 141 (2): 135–146. doi:10.1182/blood.2022016504. PMID 36122374. S2CID 252382544. Retrieved 6 October 2022.
  10. Mais, Daniel (2014). Quick compendium of clinical pathology. United States: American Society for Clinical Pathology Press. ISBN 978-0-89189-615-9. OCLC 895712380.
  11. Hill, Ben C.; Hanna, Courtney A.; Adamski, Jill; Pham, Huy P.; Marques, Marisa B.; Williams, Lance A. (2017). "Ficin-Treated Red Cells Help Identify Clinically Significant Alloantibodies Masked as Reactions of Undetermined Specificity in Gel Microtubes". Laboratory Medicine. 48 (1): 24–28. doi:10.1093/labmed/lmw062. ISSN 0007-5027. PMID 28007780.
  12. Eric Ching. "Questions and Answers on Proteolytic Enzymes Used in Blood Group Serology". Canadian Society for Transfusion Medicine. Retrieved 2021-01-28.
  13. American Association for Clinical Chemistry (15 November 2019). "Blood Typing". Lab Tests Online. Retrieved 27 January 2020.
  14. Gonsorcik, V.K. (7 August 2018). "ABO Grouping: Overview, Clinical Indications/Applications, Test Performance". Medscape. Retrieved 2 March 2020.
  15. Bacigalupo, A.; Van Lint, M. T.; M. Margiocco, D. Occhini; Ferrari, G.; Pittaluga, P. A.; Frassoni, F.; Peralvo, J.; Lercari, G.; Carubia, F.; Marmont, A. M. (1988). "Abo Compatibility and Acute Graft-Versus-Host Disease Following Allogeneic Bone Marrow Transplantation". Transplantation. 45 (6): 1091–1093. doi:10.1097/00007890-198806000-00018. ISSN 0041-1337. PMID 3289150. S2CID 39707395.
  16. Goodell, Pamela P.; Uhl, Lynne; Mohammed, Monique; Powers, Amy A. (2010). "Risk of Hemolytic Transfusion Reactions Following Emergency-Release RBC Transfusion". American Journal of Clinical Pathology. 134 (2): 202–206. doi:10.1309/AJCP9OFJN7FLTXDB. ISSN 0002-9173. PMID 20660321.
  17. Westhoff, Connie M. (2019). "Blood group genotyping". Blood. 133 (17): 1814–1820. doi:10.1182/blood-2018-11-833954. ISSN 0006-4971. PMID 30808639.
  18. "Glossary: Antibody Screen - Blood Bank Guy Glossary".

Further reading
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